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US3381006A - Certain beta-substituted-alpha-(4, 5-dimethoxy-2-nitrophenyl) acrylonitriles and 2-aminophenyl derivatives thereof - Google Patents

Certain beta-substituted-alpha-(4, 5-dimethoxy-2-nitrophenyl) acrylonitriles and 2-aminophenyl derivatives thereof Download PDF

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US3381006A
US3381006A US401635A US40163564A US3381006A US 3381006 A US3381006 A US 3381006A US 401635 A US401635 A US 401635A US 40163564 A US40163564 A US 40163564A US 3381006 A US3381006 A US 3381006A
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dimethoxy
nitrophenyl
acrylonitrile
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methanol
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John T Suh
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/337—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/57—Nitriles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Definitions

  • the compounds are useful as ult raviolet absorbers,
  • R stands for nitro or amino;
  • R stands for halophenyl, alkylphenyl, cyanophenyl, car-boxy phenyl, aminophenyl, loweralkylaminophenyl, dilower alkylaminophenyl, halomethyl-phenyl, loweralkylaminophenyl, aminoloweralkylphenyl, loweralkyl-carbonyl amino-loweralkyl-oxy phenyl, cyclohexyl, or heterocyclic aryl groups comprising five to ten membered heteroaromatics wherein the hetero atoms are one or more of thia, aza or oxa atoms, including monocyclic heteroaryls comprising five to six members having at least one sulfur, nitrogen or oxygen atom as the heteroatom, and bicyclic heteroalkyls having up to ten members and having, as one of the cyclic moie
  • pyridyl represents Z-pyridyl, 3-pyridyl or 4-pyridyl, In the same manner, N-loweralkylpiperidyl Mk1 MllUl-ltl 3,38Lt tented Apro 30, 1968 ganic materials generally, they may be used as ultraviolet,
  • absorbers in plastics and resins such as polystyrene, poly ethylene, polypropylene, polyacrylics (methacrylate resins, polyacylamides, polyacrylonitrile fibers), polyamide fibers (nylon e.g.) and polyester fibers.
  • plastics and resins such as polystyrene, poly ethylene, polypropylene, polyacrylics (methacrylate resins, polyacylamides, polyacrylonitrile fibers), polyamide fibers (nylon e.g.) and polyester fibers.
  • the absorber may be incorporated in the mixtures of monomers before polymerization to form the polymer or it may be incorporated in the polymer at any stage during its handling, as by milling into the polymer together with other compounding ingredients or during the spinning of polymers into fibers, etc,
  • novel compounds of this invention are also useful as intermediates in the preparation of novel indoles by reductive cyclization.
  • the elemental analyses as well as ultraviolet absorption, infrared absorption and nuclear magnetic resonance spectra support the assignment of the indole structures described herein.
  • novel compounds may be converted into the cor responding quaternary ammonium compounds by reac tion of the tertiary bases with alkylating agents, i.e. alkyl or aralkyl halides or esters formed by reacting alkanols with an oxygen-containing acid such as methyl iodide, ethyl bromide, propyl chloride; lower alkenyl halidesallyl bromide; dilower alkylsulfonates-dimethylsulfate, diethylsulfate; lower alkylarylsulfonates-methyl p-tolu enesulfonate or aralkyl halides--benzyl chloride.
  • alkylating agents i.e. alkyl or aralkyl halides or esters formed by reacting alkanols with an oxygen-containing acid such as methyl iodide, ethyl bromide, propyl chloride; lower alken
  • the quaternizing reaction may be performed in the presence or absence of a solvent, at room temperature or under cooling, at atmospheric pressure or in a closed vessel pressure
  • Suitable solvents for this purpose are ethers such as diethylether and tetrahydrofuran, hydrocarbons such as benzene and heptane, ketones such as acetone and butan'one, lower alkanols such as ethanol, propanol or butanol; or organic acid amides such as formamide or di methylformamide.
  • ethers such as diethylether and tetrahydrofuran
  • hydrocarbons such as benzene and heptane
  • ketones such as acetone and butan'one
  • lower alkanols such as ethanol, propanol or butanol
  • organic acid amides such as formamide or di methylformamide.
  • the resulting quaternary ammonium compounds may be converted into the corresponding quaternary ammo nium hydroxides, This may be accomplished by reaction of the quaternary ammonium halides with silver oxide, by reaction of the sulfates with barium hydroxide, by treating the quaternary salts with an anion exchanger or by electrodialysis.
  • Quaternary ammonium salts may be prepared from the resulting base by reaction with acids such as those mentioned hereinabove for the preparation of the acid addition salts or, if desired, with a mono lower alkylsulfate such as methylsulfate or ethylsulfate.
  • the quaternary ammonium compound may also be converted into another quaternary salt directly without conversion into the quaternary ammonium hydroxide.
  • the compounds of this invention may be converted to their therapeutically useful acid addition salts by reaction with an appropriate acid as, for example, an inorganic acid such as a hydrohalic acid, i.e. hydrochloric, hydrobromic or hydriodic acid; sulfuric, nitric or thiocyanic acid; a phosphoric acid; an organic acid such as acetic, propionic, glycolic, lactic, pyruvic, oxalic, malonic, succinic, maleic, picric, fumaric, mali-c, tartaric, citric, benzoic, cinnamic, mandelic, methanesulfonic, ethanesulfonic, hydroxyethanesulfonic, benzenesulfonic, p-toluenesulfonic, salicylic, p-aminosalicylic, 2-phenoxybenzoic or 2-acetoxybenzoic acid.
  • an inorganic acid such as a hydrohalic acid,
  • Example II A. solution of 6 grams of a-(4,5-dimethoxy-2-nitro phenyl)-,B-(4-pyridyl) acrylonitrile in about 80 ml. of glacial acetic acid is heated on a steam bath with 3.38 grams of iron powder under continuous stirring for sev eral hours. The mixture is then filtered. The residue from filtration ismixed with water and filtered again. The aqueous filtrate is then made basic by the addition of potassium bicarbonate. The yellow precipitate is 3-cyano 5,6-dimethoxy-2-(4-pyridyl) indole. Melting point, above 310 C.
  • Example III A mixture of 5 grams of u-(4,5-dimethoxy-2-nitro phenyl)-fi-(4-pyridy1) acrylonitrile and 1 gram of 10 percent palladium on carbon in 150 ml. of ethyl acetate is hydrogenated at room temperature for 2 /2 hours. The mixture is filtered to remove the catalyst. The solution is distilled under reduced pressure to remove the solvent. The precipitate is recrystallized from methanol to yield a (2-amino-4,5-dimethoxyphenyl)-fl-(4-pyridyl) acrylonitrile, orange needles. Melting point, 181-182 C.
  • Example IV To a refluxing solution of 22.5 grams of 4,5-dimethoxy- 2-nitrophenyl acetonitrile in 400 ml. of absolute ethanol is added in portions a solution of 11 grams 3-pyridine carboxaldehyde in 50 ml. of absolute ethanol, and 8 ml. of piperidine. The resulting solution is allowed to reflux for 2 hours and cooled. The bright yellow product a-(4,5-- dimethoxy-Z-nitrophenyl)-fi-(3-pyridyl) acrylonitrile crystallizes from the solution. Melting point, 204 C.
  • Example V A mixture of grams of a-(4,5-dimethoxy-2-nitrophenyl)-/S-(3-pyridyl) acrylonitrile and percent palladium on carbon in a mixture of ethyl acetate and ethanol is shaken with hydrogen for 1 hour. The catalyst. is filtered off and the filtrate is distilled in vacuo to remove the solvent. The product is a-(2-amino-4,S-dimethcxyphenyl)- fl-(3-pyridine) acrylonitrile. Melting point, 130 C.
  • Example VI A solution of 12 grams of u-(4,5-dimeth0xy-2-nitrophenyl)-fl-(3 pyridyl) acrylonitrile in approximately 90 ml. of glacial acetic acid is heated on a steam bath with 6.76 grams of iron powder under continuous stirring for several hours. The mixture is filtered and. the residue is 4 mixed with Water and filtered again. Both the acetic acid filtrate and the aqueous filtrate are made basic by the addition of potassium bicarbonate. The product obtained is 3-cyano-5,6-dimethoxy-2-(3-pyridyl) indole. Melting point, 238239 C.
  • Example VII A 10 gram sample of a-(4,5-dimethoxy-2-nitrophenyl)- fl-(3-pyridyl) acrylonitrile is added to 300 ml. of 1,2di methoxyethane containing 9.1 grams of methyl iodide. The reaction mixture is refluxed for 1 hour with stirring and filtered to give an orange precipitate of 3(f3-cyano- 4,5 dimethoxy-Z-nitrostyryl)-1-methylpyridinium iodide which is recrystallized from methanol to yield yellow needles. Melting point, 206207 C.
  • Example IX To a warm solution of 30 grams of 4,5-dimethoxy-2" nitrophenylacetonitrile in 300 ml. of ethanol, 25 grams of p-diethylaminobenzaldehyde is added. The solution is treated with 9.45 ml. of piperidine and allowed to reflux for 6 hours. The reaction mixture is cooled and filtered to yield a bright orange precipitate. The precipitate is recrystallized from methanol to give fluffy orange plates of a- (4,5 dimethoxy 2-nitrophenyl)-fl-(4-diethylaminophenyl) acrylonitrile. Melting point, 123-124 C.
  • Example XI To a refluxing solution of 10 grams of -(4,5-dimethoxy Z-nitrophenyl)-fl-(4-diethylaminophenyl) acryloni trile in 250 ml. of glacial acetic acid is added in portions 294 grams of iron powder. The resulting reaction mixture is allowed to reflux for 2 /2 hours and is then filtered. The filtrate is distilled under diminished pressure. The residue is treated with 150 ml. of water, filtered and the residue and filtrate (from filtration) are treated with 100 ml. of methanol and 10 percent sodium hydroxide solu tion.
  • the solid product is filtered and recrystallized from hot boiling methanol with the addition of water to yield 3-cyano-5,6-dimethoxy Z-(p-diethylaminophenyl) indole.
  • the hydrochloric acid addition salt is prepared by reacting B-cyano 5,6-dimethoxy-2-(p-diethylaminophenyl) dole with hydrogen chloride in ether.
  • other acid addition salts such as the fumarate, maleate and hexamate salts are prepared by using the corresponding acid in ether solution.
  • Example X-II n A mixture of 3.74 grams of ut-(4,5-dimethoxy-2-nitrophenyl) 'fl M-diethylaminopheuyl) acrylonitrile and l gram of percent palladium on carbon in 150 ml. of ethyl acetate is hydrogenated at room temperature for 4 hours. Removal of the solvent and recrystallization of the residue from methanol gives a (2-ami-no-4,5-dimeth .OXyphenyl-B-(4-diet-hylaminophenyl) acrylonitrile. Melt ing point, 146-147 C.
  • UV. absorption in methanol 219 III/J, (e 28,000); 242 m (e 16,300); 359 my. (e 19,900),
  • Example XXIX To a refluxing solution of 24 grams of p-(p-chlow phenyl)-a-(4,5-dimethoxy-2-nitrophenyl) acrylonitrile in 200 ml. of glacial acetic acid is added in portions 8 grams of iron powder The reaction mixture is refluxed for 3 to 4 hours, cooled and then filtered. The residue is washed with hot methanol and boiling water and crystallized from methanol to give 3-cyano-2-(pch1orophenyl)-5,6-d-imethoxyindole. Melting point, 284-286" C,
  • Example XXXV Using the procedure of Example XXVIII and replacing the p-chlorobenzaldehyde with an equivalent amount of p-trifluoromethylbenzaldehyde, the product recovered is B-(ptrifluoromethylphenyl)-a-( 4,5 dimethoxy-Z-nitrophenyl) acrylonitrile.

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Description

CERTAIN fi-SUBSTITUTED-a-(4,5-DIMETHOXY- Z-NITROPHENYL) ACRYLONITRILES AND 2- AMINOPHENYL DERIVATIVES THEREOF John T. Suh, Mequon, Wis., assignor to McNeil Labora- 5 tories, Incorporated, a corporation of Pennsylvania No Drawing. Filed Oct. 5, 1964, Ser. No. 401,635 7 Claims. (Cl. 260-240) ABSTRACT OF THE DISCLOSURE The compounds of this invention are of the type of ,9 (heterocyclic substituted) Ot- (4,5 dimethoxy u 2 nitrophenyl)acrylonitriles and fi-(heterocyclic substi tuted) -a-(4,S-dimethoxy-2-aminophenyl acrylonitriles, in which the heterocyclic members are pyrrolyl, N-1ower=- alkylpyrrolyl and N-loweralkyl-piperidyl, The compounds are useful as ult raviolet absorbers,
This invention relates to a new series of compounds. More particularly it concerns certain 13-substituted-a-(4,5= dimethoxy-Z-nitrophenyl) acrylonitriles and certain fi substituted 0: (4,5 dimethoxy 2 aminophenyl) acrylonitriles which may be represented as follows:
C1130 -C=CE-RQ 1 N C1130 Rr In the above formula R stands for nitro or amino; R stands for halophenyl, alkylphenyl, cyanophenyl, car-boxy phenyl, aminophenyl, loweralkylaminophenyl, dilower alkylaminophenyl, halomethyl-phenyl, loweralkylaminophenyl, aminoloweralkylphenyl, loweralkyl-carbonyl amino-loweralkyl-oxy phenyl, cyclohexyl, or heterocyclic aryl groups comprising five to ten membered heteroaromatics wherein the hetero atoms are one or more of thia, aza or oxa atoms, including monocyclic heteroaryls comprising five to six members having at least one sulfur, nitrogen or oxygen atom as the heteroatom, and bicyclic heteroalkyls having up to ten members and having, as one of the cyclic moieties, a five=to-six membered heteroaromatic ring with at least one sulfur, nitrogen or oxygen atom, and including specifically pyridyl, quinolyl, imidazolyl, pyrazinyl, pyrrolyl, thienyl, furyl, thiazolyl, thiadiazolyl, pyrazolyl, oxazolyl, pyrimidinyl, and N alkylated derivatives thereof, Acid addition salts, such. as the hydrochloride, fumarate, maleate and hexamate and loweralkyl quaternary ammonium derivatives of those fl= substituted acrylonitriles containing a basic nitrogen in the R position are also included in the invention,
Compounds of the structure represented by the formula wherein R is nitro are prepared by condensing 4,5 dimethoxy-Z-nitrophenyl acetonitrile with an aldehyde se lected from the group consisting of halophenyl, cyclohexyl, aminophenyl, loweralkylaminophenyl, di-loweralkyl aminophenyl, loweralkyl-carbonylamino-lower alkyl, cyanophenyl, trihalomethylphenyl, thienyl, furyl, pyrrolyl, oxyphenyl, pyridyl, and N-loweralkyl piperidyl aldehydes in the presence of a catalytic amount of piperidine,
Compounds of the structure represented by the formula wherein R is amino are prepared by hydyogenating the fi-substituted-a-(4,idimethoxy-Z-nitrophenyl) acrylonitriles at room temperature in the presence of percent palladium on carbon, using ethyl acetate as the solvent for the reaction. Other suitable methods for the reduction of the nitro group to the amino group may be employed;
As used herein, pyridyl represents Z-pyridyl, 3-pyridyl or 4-pyridyl, In the same manner, N-loweralkylpiperidyl Mk1 MllUl-ltl 3,38Lt tented Apro 30, 1968 ganic materials generally, they may be used as ultraviolet,
absorbers in plastics and resins, such as polystyrene, poly ethylene, polypropylene, polyacrylics (methacrylate resins, polyacylamides, polyacrylonitrile fibers), polyamide fibers (nylon e.g.) and polyester fibers. In the latter use, the inclusion of 0.01 to 5 percent of the absorber, based on the polymer weight, is sufiicient to render protection against ultraviolet light, such as in plastic film or light filters, The absorber may be incorporated in the mixtures of monomers before polymerization to form the polymer or it may be incorporated in the polymer at any stage during its handling, as by milling into the polymer together with other compounding ingredients or during the spinning of polymers into fibers, etc,
The novel compounds of this invention are also useful as intermediates in the preparation of novel indoles by reductive cyclization. The reductive cyclization of the 3- substituted-4,5-=dimethoxy-2-nitrophenyl acrylonitriles is desirably achieved by adding iron powder to a refluxing solution of the nitrile in a glacial acetic acid and allowing the reaction mixture to reflux for 2 to 5 hours, The solvent is distilled under diminished pressure and the crude prod= not is purified by recrystallization, The elemental analyses as well as ultraviolet absorption, infrared absorption and nuclear magnetic resonance spectra support the assignment of the indole structures described herein.
The novel compounds may be converted into the cor responding quaternary ammonium compounds by reac tion of the tertiary bases with alkylating agents, i.e. alkyl or aralkyl halides or esters formed by reacting alkanols with an oxygen-containing acid such as methyl iodide, ethyl bromide, propyl chloride; lower alkenyl halidesallyl bromide; dilower alkylsulfonates-dimethylsulfate, diethylsulfate; lower alkylarylsulfonates-methyl p-tolu enesulfonate or aralkyl halides--benzyl chloride. The quaternizing reaction may be performed in the presence or absence of a solvent, at room temperature or under cooling, at atmospheric pressure or in a closed vessel pressure, Suitable solvents for this purpose are ethers such as diethylether and tetrahydrofuran, hydrocarbons such as benzene and heptane, ketones such as acetone and butan'one, lower alkanols such as ethanol, propanol or butanol; or organic acid amides such as formamide or di methylformamide. When lower alkyl halogenides are used as quaternizing agents, diethyl ether and benzene are the preferred solvents,
The resulting quaternary ammonium compounds may be converted into the corresponding quaternary ammo nium hydroxides, This may be accomplished by reaction of the quaternary ammonium halides with silver oxide, by reaction of the sulfates with barium hydroxide, by treating the quaternary salts with an anion exchanger or by electrodialysis. Quaternary ammonium salts may be prepared from the resulting base by reaction with acids such as those mentioned hereinabove for the preparation of the acid addition salts or, if desired, with a mono lower alkylsulfate such as methylsulfate or ethylsulfate. The quaternary ammonium compound may also be converted into another quaternary salt directly without conversion into the quaternary ammonium hydroxide. Thus, a qua= ternary ammonium iodide may be reacted with freshly prepared silver chloride to yield the quaternary ammonima m man/F405 DEV um chloride, or the quaternary ammonium iodide may be converted into the corresponding chloride by treatment with hydrochloric acid in anhydrous methanol.
The compounds of this invention may be converted to their therapeutically useful acid addition salts by reaction with an appropriate acid as, for example, an inorganic acid such as a hydrohalic acid, i.e. hydrochloric, hydrobromic or hydriodic acid; sulfuric, nitric or thiocyanic acid; a phosphoric acid; an organic acid such as acetic, propionic, glycolic, lactic, pyruvic, oxalic, malonic, succinic, maleic, picric, fumaric, mali-c, tartaric, citric, benzoic, cinnamic, mandelic, methanesulfonic, ethanesulfonic, hydroxyethanesulfonic, benzenesulfonic, p-toluenesulfonic, salicylic, p-aminosalicylic, 2-phenoxybenzoic or 2-acetoxybenzoic acid.
The following examples are intended to illustrate, but not to limit, the scope of the invention.
Example I A solution of 6.59 grams of 4,5-dimethoxy 2-nitrophenyl acetonitrile and 4.1 grams of 4-pyridine carboxaldehyde in 250 ml. of boiling absolute alcohol is treated with 3.13 ml. of piperidine. The solution is boiled for 2 /2 hours and allowed to stand at room temperature for 2. days. A yellow precipitate is obtained. The mixture is filtered and the precipitate collected to yield a=-(4,5-di methoxy-Z-nitrophenyl)-fl-(4-pyridyl) acrylonitrile. Melt ing point, 201 C.
Example II A. solution of 6 grams of a-(4,5-dimethoxy-2-nitro phenyl)-,B-(4-pyridyl) acrylonitrile in about 80 ml. of glacial acetic acid is heated on a steam bath with 3.38 grams of iron powder under continuous stirring for sev eral hours. The mixture is then filtered. The residue from filtration ismixed with water and filtered again. The aqueous filtrate is then made basic by the addition of potassium bicarbonate. The yellow precipitate is 3-cyano 5,6-dimethoxy-2-(4-pyridyl) indole. Melting point, above 310 C.
Example III A mixture of 5 grams of u-(4,5-dimethoxy-2-nitro phenyl)-fi-(4-pyridy1) acrylonitrile and 1 gram of 10 percent palladium on carbon in 150 ml. of ethyl acetate is hydrogenated at room temperature for 2 /2 hours. The mixture is filtered to remove the catalyst. The solution is distilled under reduced pressure to remove the solvent. The precipitate is recrystallized from methanol to yield a (2-amino-4,5-dimethoxyphenyl)-fl-(4-pyridyl) acrylonitrile, orange needles. Melting point, 181-182 C.
Example IV To a refluxing solution of 22.5 grams of 4,5-dimethoxy- 2-nitrophenyl acetonitrile in 400 ml. of absolute ethanol is added in portions a solution of 11 grams 3-pyridine carboxaldehyde in 50 ml. of absolute ethanol, and 8 ml. of piperidine. The resulting solution is allowed to reflux for 2 hours and cooled. The bright yellow product a-(4,5-- dimethoxy-Z-nitrophenyl)-fi-(3-pyridyl) acrylonitrile crystallizes from the solution. Melting point, 204 C.
Example V A mixture of grams of a-(4,5-dimethoxy-2-nitrophenyl)-/S-(3-pyridyl) acrylonitrile and percent palladium on carbon in a mixture of ethyl acetate and ethanol is shaken with hydrogen for 1 hour. The catalyst. is filtered off and the filtrate is distilled in vacuo to remove the solvent. The product is a-(2-amino-4,S-dimethcxyphenyl)- fl-(3-pyridine) acrylonitrile. Melting point, 130 C.
Example VI A solution of 12 grams of u-(4,5-dimeth0xy-2-nitrophenyl)-fl-(3 pyridyl) acrylonitrile in approximately 90 ml. of glacial acetic acid is heated on a steam bath with 6.76 grams of iron powder under continuous stirring for several hours. The mixture is filtered and. the residue is 4 mixed with Water and filtered again. Both the acetic acid filtrate and the aqueous filtrate are made basic by the addition of potassium bicarbonate. The product obtained is 3-cyano-5,6-dimethoxy-2-(3-pyridyl) indole. Melting point, 238239 C.
Example VII A 10 gram sample of a-(4,5-dimethoxy-2-nitrophenyl)- fl-(3-pyridyl) acrylonitrile is added to 300 ml. of 1,2di methoxyethane containing 9.1 grams of methyl iodide. The reaction mixture is refluxed for 1 hour with stirring and filtered to give an orange precipitate of 3(f3-cyano- 4,5 dimethoxy-Z-nitrostyryl)-1-methylpyridinium iodide which is recrystallized from methanol to yield yellow needles. Melting point, 206207 C.
U.V. absorption in methanol 219 m (e 29,500) g 255 m (e 18,200); 270 m (6 16,400); 297 mu (6 12,700).
Example VIII To a. mixture of 3 grams of 4-(B-cyano-4,5-d imethoxy= 2-nitrostyryl)-1-methylpyridinium iodide in m1. of methanol is added in portions 1.1 grams of sodium bore hydride and the reaction mixture is allowed to stand at room temperature for 1 hour while stirring. During this period the color of the reaction mixture changes slowly .from dark brown to light brown. The methanol solution is distilled in vacuo and ml. of ice water is" added to the residue. The water insoluble residue a-(4,5-dimethoxy-2-nitrophenyl)-fl-(1,2,3,6-tetrahydro l-methyl 4 pyridine) acrylonitrile is isolated by filtration and dried in air at room temperature. Melting point, 136 C.
Example IX .To a warm solution of 30 grams of 4,5-dimethoxy-2" nitrophenylacetonitrile in 300 ml. of ethanol, 25 grams of p-diethylaminobenzaldehyde is added. The solution is treated with 9.45 ml. of piperidine and allowed to reflux for 6 hours. The reaction mixture is cooled and filtered to yield a bright orange precipitate. The precipitate is recrystallized from methanol to give fluffy orange plates of a- (4,5 dimethoxy 2-nitrophenyl)-fl-(4-diethylaminophenyl) acrylonitrile. Melting point, 123-124 C.
Example XI To a refluxing solution of 10 grams of -(4,5-dimethoxy Z-nitrophenyl)-fl-(4-diethylaminophenyl) acryloni trile in 250 ml. of glacial acetic acid is added in portions 294 grams of iron powder. The resulting reaction mixture is allowed to reflux for 2 /2 hours and is then filtered. The filtrate is distilled under diminished pressure. The residue is treated with 150 ml. of water, filtered and the residue and filtrate (from filtration) are treated with 100 ml. of methanol and 10 percent sodium hydroxide solu tion. The solid product is filtered and recrystallized from hot boiling methanol with the addition of water to yield 3-cyano-5,6-dimethoxy Z-(p-diethylaminophenyl) indole. The hydrochloric acid addition salt is prepared by reacting B-cyano 5,6-dimethoxy-2-(p-diethylaminophenyl) dole with hydrogen chloride in ether. In a similar manner other acid addition salts such as the fumarate, maleate and hexamate salts are prepared by using the corresponding acid in ether solution.
Example X-II n A mixture of 3.74 grams of ut-(4,5-dimethoxy-2-nitrophenyl) 'fl M-diethylaminopheuyl) acrylonitrile and l gram of percent palladium on carbon in 150 ml. of ethyl acetate is hydrogenated at room temperature for 4 hours. Removal of the solvent and recrystallization of the residue from methanol gives a (2-ami-no-4,5-dimeth .OXyphenyl-B-(4-diet-hylaminophenyl) acrylonitrile. Melt ing point, 146-147 C.
Example XIIII A solution of 30 grams of 4,S-dimethoxy-Z-nitrophenyl acetonitrile, 23 grams of p-dimethylaminobenzaldehyde and 10 ml. of piperidine in 400 ml. of methanol is allowed to reflux for 3 hours. Upon cooling and filtering the mixture, a-(4,5-dimethoxy Q 2-nitrophenyl)-fi-(p-dimethyl= aminophenyl) acrylonitrile is obtained. Melting point, 181 C.
Example XIV To a refluxing solution of 16 grams of a-(4,5-dimeth= oxy Z-nitrophenyl) fl-(p-dimethylaminophenyl) acrylo= nitrile in 200 ml. of acetic acid is added in portions 5.1 grams of iron powder and the reaction mixture is allowed to reflux for 6 hours. The reaction mixture is filtered and the residue is washed with methanol twice to yield 3-= cyano 5,6-dimethoxy=2- (p-dimethylaminophenyl) indole. Melting point, 265-266 C.
Example XV To a warm solution of 22 grams of 4,5-dimethoxy-2-= nitrophenylacetonitrile in 400 ml. of absolute ethanol is added 11 grams of pyridine-2-carboxaldehyde in 50 ml. of absolute alcohol and 8 ml. of piperidine. The reaction mixture is refluxed for 2 hours and is thereafter cooled and filtered to give u-(4,5-dimethoxy-Z-nitrophenyl) 3-2= pyridylacrylonitrile. Recrystallization from ethyl acetate gives pure material. Melting point, 187-189 C.
Example XVI To a refluxing solution of '30 grams of 4,5-=dimethoxy- 2-nitrophenylacetonitrile in 250 ml. of absolute methanol is added 33 grams of p-2-diethylaminoethoxybenzaldehyde and 10 ml. of piperidine. The resulting mixture is refluxed for 6 hours, cooled, filtered to yield a solid which is recrystallized from methanol to obtain fl-[p-(2-diethyk aminoethoxy) phenyl] -a-(4,5-dimethoxy 2nitropheny1) acrylonitrile. Melting point, 105 C.
Example XVII To a refluxing solution of 20.5 grams of tI-[p-(Z-diethyl-= aminoethoxy) phenyl]-a-(4,5-dimethoxy 2 nitrophenyl) acrylonitrile in 200 ml. of acetic acid is added in. por= tions, 5.6 grams of iron powder. The reaction mixture is refluxed for 4 hours. The mixture is filtered and the filtrate is distilled in vacuo. The residue is treated with 20.0 ml. of water and 30 percent of sodium hydroxide to make the solution basic and filtered. The product obtained is 3-cyano 2-[p-(2-diethylaminoethoxy) phenyl]-5,6-di-= methoxyindole which is recrystallized several times from dilute methanol. Melting point, 165 C.
Example XVIII A solution of grams of 4,S-dimethoxy=2-nitrm phenyl acetonitrile and 15 grams of pyrrole-2-car-boxalde hyde in about 250 ml. of absolute ethanol is treated with 7.23 ml. of piperidine under refluxing. The refluxing is continued for '1 hour. The mixture is filter-ed to yield a solid which is recrystallized from methanol-ethanol to give u-(4,S-dimethoxyJ-nitrophenyl) a ,8 (2 Q pyrrolyl) acrylonitrile, red crystals. Melting point, 193-4194 C.
UV. absorption in methanol: 218 m (e 16,600); 247 mu (6 11,100); 337 mu (e 24,400).
Example XIX A solution of 4 15 grams of 4,5-dimethoxy 2-n-itrophenylacetonitrile and 9.5 grams of N-met-hylpyrroie L carboxaldehyde in about 250 ml. of absolute ethanol is treated with 7.23 ml. of piperidine and refluxed for ap-= 6 proximately 4 hours. The mixture is filtered to yield an orange precipitate of te l2-nitro-4.5-dimethoxyphenyl)li tlamethyllpyrrolyll acrylonitride. Melting point, 182: 183 Cd Example XXJ A solution of 4.68 grams of 4,5 dimethoxy=2-nitro phenylacetonitrile and 3.04 grams of 'z thiophenecarbox minutes. The reaction m-hrture is then filtered to yield a solid which is recrystallized firom methanol to give silvery white needles of 3-cyano-5,6-dimethoxy-2-(2- thienyl) indole. Melting point 209-210 C.
Example XXII To a warm solution of 30 grams of 4,5-dimethoxy-2- nitrophenylacetonitrile in 300 ml. of absolute ethanol, 15 grams of iurfural and 9.45 grams of piperidine (catalyst) are added. The reaction solution is refluxed for 1 /2 hours, cooled and filtered to yield w-(2-Illt10-4 .5= dimethoxyphenyl) =p"(2.-'furyl) acrylonitrile. Melting point, 181418? C.
UV. absorption in methanol: 213 nm (e 12,200); 2.44 mg. (e 12.900 3 16 mp1. (e 25.600).
Example XXIII A solution of 17.7 grams of a (2-nitro-4,5-dimethoxy= phenyl)-fl=(2=furyl) acrylonitrile in 300 ml. of glacial acetic acid is stirred with 6.57 grams of iron powder under refluxing for about 2 /2 hours. The reaction is allowed to cool and is filtered. Evaporation of the filtrate leaves a guru which crystallizes upon treatment with water. Re= crystallization of the solid from aqueous ethanol gives 3- cyano=2-(2-furyl)-5,'6-dimethoxyindo1e. Melting point,
UN. absorption in methanol: 237 mu lie-19,100); 336 my. (s 299400).
Example XXIV To a refluxing solution of 10 grams of 4,5dimethoxy- 2 nitrophenylacetonitrile in 200 ml. of methanol is added in portions 7 grams of cyclohexauecarboxyaldehyde and 3 ml. of piperidine. The mixture is allowed to reflux for 6 hours. The reaction mixture is cooled and the solid product precipitated is filtered and crystallized from methanol to give fi-cyclohexyhm(4,5=dimethoxy=2-nitrre phenyl) acrylonitrile. Melting point, 161 C.
UV. absorption in methanol: 248 mu (e 12.400); 295, 342 mu.
Example XXV To a refluxing solution of 22.5 grams of 1.8cyclohexyl a(4,5-dime'thoxy-Q-nitrophenyl) acrylonitrile in 200 ml. of acetic acid is added in portions 8.4 grams of iron powder. The resulting mixture is refluxed for 6 hours. The reaction mixture is filtered and the filtrate is evap orated under diminished pressure to give a residue which. is recrystallized from ethyl acetate-hexane to obtain 3 cyano-2-cyc'lohexyl-5,6=dimethoxyindo1e. Melting point,
Example To In warm solution of 30 grams of 4,S-dimethoxy-2- nitrophenylacetonitrile in 300 ml. of absolute ethanol, 20 grams of 4-cyano'benzaldehyde and 9.45 ml. of piperidine are added. The reaction mixture is refluxed for 3 hours. The resulting mixture filtered to yield a. hright yellow productwhich is crystallized from methanol to give o2-(2'- nitro-4,S-dimethoxyphenyl) 4-cyanopl1enyl) acry1oni= trile. Melting point, 2'142;l5 (3.
UV. absor tion in methanol: 246 mp. (8 14,200); 289 me (e 26,600),
Example XXVII A solution of 5 grams of a-(2-nitro-4,5-dimethoxy phenyl)-B-(4-cyanophenyl) acrylonitrile in 17 5 11116 of acetic acid is stirred with 1.66 grams of iron powder under refluxing conditions for approximately 2 hours. The re action mixture is cooled and filtered: The solid product is recrystallized from methanol to yield 3cyano-5,6-dimethoxy=2 (4 cyanophenyljl indole. Melting point: 2:83" C.
UV. absorption in methanol: 219 III/J, (e 28,000); 242 m (e 16,300); 359 my. (e 19,900),
Example XXVHI To a refluxing solution of 21 grams of 4,5-dimet1hoxy' Z-nitrophenylacetonitrile in 200 ml. of methanol is added in portions, 14 grams of p-ch-lorohenzaldehyde in 100 ml of methanol and 5 ml. of piperidine. Elhe mixture is refluxed for 4 hours, The reaction mixture is cooled and the solid product is filtered and recrystallized from methanol to give fl-(p-ch'lorophenyl)-a-(4,5-dimethoxy-2= nitrophenyl) acrylonitrile. Melting point," 176.5477 C.
UN. absorption in methanol: 295 nip. (6 259800); 223 my. (e 18,700).
Example XXIX To a refluxing solution of 24 grams of p-(p-chlow phenyl)-a-(4,5-dimethoxy-2-nitrophenyl) acrylonitrile in 200 ml. of glacial acetic acid is added in portions 8 grams of iron powder The reaction mixture is refluxed for 3 to 4 hours, cooled and then filtered. The residue is washed with hot methanol and boiling water and crystallized from methanol to give 3-cyano-2-(pch1orophenyl)-5,6-d-imethoxyindole. Melting point, 284-286" C,
U.V. absorption in methanol: 331 mp (e 22,000); 236 mu (e 24,800).
Example XXX A mixture of 10 grams of B-=(p-chlorophenyl)=a-(4.5 dimethoxy=2-nitrophenyl) acrylonitrile and 1 gram of palladium on carbon in 175 ml. of l,2-dirnethoxyethane is shaken with hydrogen at room temperature. The theoreti= cal amount of hydrogen is taken up within 2 hours. The reaction mixture is filtered. The filtrate is evaporated in vacuo and the residue is triturated with petroleum ether and ethanol. A bright orange product, t-(2-amino-4,5-= dimethoxyphenyD-B-(p-chlorophenyl) acrylonitrile is ob tained which is crystallized from benzene. Melting point, 112-115 C.
Example XXXI Using the procedure of Example XXVIII and replac ing the p chlorobenzaldehyde with an equivalent amount of p-methylaminobenzaldehyde, the productrecovered is B-(p methylaminophen yl not a (4,5 dimethoxy-2-nitro= phenyl) acrylonitrile 8 v Example XXXIV Using the procedure of Example XXIX and replacing the fl-(p m chlorophenyl)-w(4,5 dimethoxy-Z-nitrophenyl) acrylonitrile with an equivalent amount of fl-(p= methylaminophenyl.)-a-(4,5 n dimethoxy 2 nitrophenyl) acrylonitrile. the product. recovered is 3-cyano-2-(pmethylaminophenyl) 5,6-dimethoxyindole.
Example XXXV Using the procedure of Example XXVIII and replacing the p-chlorobenzaldehyde with an equivalent amount of p-trifluoromethylbenzaldehyde, the product recovered is B-(ptrifluoromethylphenyl)-a-( 4,5 dimethoxy-Z-nitrophenyl) acrylonitrile.
Example XXXVI Using the procedure of Example XXIX and replac ing the pr n (p chlorophenyhu- (4,5-dimethoxy-2-nitro phenyl) acrylonitrile with an equivalent amount of p (p u trifluoromethylphenyl) a a (4,5-dimethoxy-2-nitro= phenyl) acrylonitrile the product recovered is 3-cyano-2= (p-trifluoromethylphenyl)-5,6-dimethoxyindole= Example XXXV II Using the procedure of Example III and replacing the a-(4,5-dimethoxy-Z-nitrophenyl)-B-(4-pyridyl) acry lontrile with an equivalent amount of one of the fol= lowing: w-(4,5-dimethoxy-Z-nitrophenyl)-fi-(3-pyridyl) acrylonitrile a- (4,5 -dimethoxy-2-nitrophenyl) 9- (2-pyridyl) acrylonitrile m-(4,S-dimethoxy=2-nitrophenyl)-;8-(dirnethylaminophenyl) acrylonitrile a.- (4,5 =dimethoxy-2-nitro phenyl) -B- p- (Z-diethylaminm ethoxy) phenyl] acrylonitrile w(4,5-dimethoxy-Z-nitrophenyl)-p-(2-pyrrolyl) acrylo nitrile a,-(4,5-dimethoxy-2 nitrophenyl)-fl-(1-methyl-2-pyrrolyl) acrylonitrile a(4.5-dimethoxy=2=nitrophenyl)=p-(2-thienyl) acrylonitrile a(4 5-dimethoxy=2-nitrophenyl)-,B-(2furyl) aerylo= nitrile w(4,5-dimethoxy-Z-nitrophenyl)-j3-(cyclohexyl) acrylonitrile a-(4,S-dimethoxy-2=nitrophenyl)-fl-(4-cyanophenyl) acry= lonitrile a(4,5-dim.ethoxy 2nitrophenyl)-fi-(p-methylamino= phenyl) acrylonitrile a (4,5 -dimethoxy 2-nitrophenyl) 49- p-trifiuoromethyh phenyl) acrylonitrile a(4,5-dimethoxy=2-nitrophenyl)-fl (p-aminophenyl) acrylonitrile and corresponding product recovered is:
st(4,5-dimethoxy=2 =aminophenyl) -;8-( 3-pyridy1) acrylonitrile a-(4,5=dimethoxy=2-aminophenyl)-j3-(2-pyridy1) acrylo nitrile w (4,5=dimethoxy=2-aminophenyl) -fip-dimethylamino phenyl) acrylonitrile w (4,5-dimethoxy=-2-aminophenylIt =p= p- (2-diethylamino= ethoxy) phenyl] acrylonitrile w(4,5-dimethoxy-2-aminophenyl)-p-(2=pyrrolyl) acrylonitrile w (4,5-=dimethoxy=2-aminophenyl) =fl= 1-methyl-2=pyrollyl) acrylonitrile a-(4,5 dimethoxy-2-aminophenyl)-fi-(Z-thienyl) acrylo nitrile w(4,5=dimethoxy=2-aminophenyl)p-(Z-furyl) acrylonitrile w (4,5 dimethoxy=2-aminophenyl) p (cyclohexyl) acrylonitrile 9 m tflj dimethoxy-i-arni nophenyl -fil-cyanophenyl.)
acrylonitrile a-(4,S-dirnethoxy-2aminophenyl)-fl-(p-methy1aminophenyl) acrylonitrile a- 4,S-dimethoxy-Z-aminophenyl =flp-trifluoromethyi phenyl) acrylonitrile a-(4,5-dimethoxy-Z-aminophenyl) fl-(p-aminophenyl) acrylonitrile Example XXXVIII A solution of one of the following:
u-(4,5-dimethoxy-2-nitrophenyl)p=(3-pyridyl) acrylo= nitrile a-(4,5-dimethoxy-2-nitropheny1)-fi-(4-pyridyl) acry10- nitrile a- (4,5-dimethoxy-2-nitropheny1) 8- (Z-pyridyl) acrylo= nitrile a-(4,S-dimethoxy-Z-nitrophenyl)--(4-diethy1amino= phenyl) acrylonitrile a- (4,5-dimethoxy-2-nitrophenyl) =-;8- [p- (Z-diethylamino ethoxy) phenyl] acrylonitrile a- (4, 5-dirnethoxy-2-nitropheny1) =fl-2 (p-diethylaminophenyl) acrylonitrile oc- (4,5 -dimethoxy 2-nitrophenyl) 8 a-aminophenyl) acrylonitrile oc- (4,5-dimethoxy-2-nitropheny1) 3- (p-methylamino= phenyl) acrylonitrile and an equivalent amount of methyl iodide in dimethoxy ethane is allowed to reflux for 4 hours The corresponding methiodide derivative is recovered Example XXXIX A solution of one of the following:
10 and an equivalent; amount of methyl iodide in dimethoxy" ethane is refluxed for four hours, The corresponding methiodide is recovered,
Example XL Acid addition salts of the B-substituted-a-(4,5-dimethoxy=2-nitrophenyl) acrylontriles and the 5-substituted-a- (4,5 dimethoxy 2 a aminophenyl) acrylonitn'les of this invention wherein a basic nitrogen is present are prepared by reacting the nitrile in a suitable solvent such as ether with the acid, for example hydrogen chloride in ethert Other suitable acids are employed in place of hydrogen chloride in ether to produce corresponding acid addition salts What is claimed is? Ila (ac-(4,5 dimethoxy 2- nitrophenyl) B a (1,2,3,6- tetrahydro-1-methyl-4-pyridyl) acrylonitrile.
2. d-(4,5 dimethoxy 2 a aminophenyl) p e (1-meth= yl-4-piperidyl) acrylonitrile,
3. tit-(4,5 dimethoxy 2 nitrophenyl) B (2-pyrroyl) acrylonitrilen 4. rat-(4,5 dimethoxy 2 nitrophenyl) 3 (1-rnethyl-= 2-pyrroyl) acrylonitrileq 5, (It-(4,5 dimethoxy 2. nitrophenyl) g (2-thien= yl) acrylonitrile,
6. a-(4,5 dimethoxy m 2 u nitrophenyl) 5 (Z-furyl) acrylonitrile,
7 A. member of the group consisting of a ii-substituted a (4,5 dimethoxy m 2 nitrophenyl)acrylonitrile and a B-substituted J a: (4,5 dimethoxy 2 aminophenyl) acrylonitrile having the formula wherein R is a member of the group consisting of nitro and amino, and R is a member of the group consisting of pyrrolyl, N-lower alkylpyrrolyl, and N-lOWer alkyl-- piperidyl, and the non-toxic acid addition salt and lower alkyl quaternary ammonium derivative thereof,
References Cited Walker: I, Chem Soot, vols 78, pp- 3698-3701. (1956), QB 1 A 5:
Lavagnino: J Org; Chem Soc vol; 22, pp 457-458 (1957), QD 241 L 6,
JOHN D RANDOLPH Primary Examiners WALTER At MODANCE Examiner.
H; 11 IMOATZ, Assistant Examiner
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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3502707A (en) * 1967-09-11 1970-03-24 Mcneilab Inc Beta-(cyclohexyl and substituted phenyl)-alpha-(4,5-dimethoxy-2-nitro- or aminophenyl) acrylonitriles
US4284621A (en) * 1978-04-18 1981-08-18 Bayer Aktiengesellschaft Agents for protection against light
US4950467A (en) * 1986-11-14 1990-08-21 Ici Americas Inc. Ultraviolet radiation absorbing compositions
WO1992018481A1 (en) * 1991-04-16 1992-10-29 Rhone-Poulenc Rorer International (Holdings), Inc. Styryl-substituted heteroaryl compounds which inhibit egf receptor tyrosine kinase
US5656655A (en) * 1994-03-17 1997-08-12 Rhone-Poulenc Rorer Pharmaceuticals, Inc. Styryl-substituted heteroaryl compounds which inhibit EGF receptor tyrosine kinase
WO2006055565A2 (en) * 2004-11-19 2006-05-26 Schering-Plough Ltd. Control of parasites in animals by the use of parasiticidal 2-phenyl-3-(1h-pyrrol-2-yl) acrylonitrile derivatives
US20100261698A1 (en) * 2008-06-27 2010-10-14 Christopher Adams Organic compounds
CN110386881A (en) * 2018-04-19 2019-10-29 中国科学院昆明植物研究所 Diaryl ethylene compounds and its pharmaceutical composition and its application

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Publication number Priority date Publication date Assignee Title
US3502707A (en) * 1967-09-11 1970-03-24 Mcneilab Inc Beta-(cyclohexyl and substituted phenyl)-alpha-(4,5-dimethoxy-2-nitro- or aminophenyl) acrylonitriles
US4284621A (en) * 1978-04-18 1981-08-18 Bayer Aktiengesellschaft Agents for protection against light
US4950467A (en) * 1986-11-14 1990-08-21 Ici Americas Inc. Ultraviolet radiation absorbing compositions
AU670026B2 (en) * 1990-04-16 1996-07-04 Rhone-Poulenc Rorer International (Holdings) Inc. Styryl-substituted heteroaryl compounds which inhibit EGF receptor tyrosine kinase
WO1992018481A1 (en) * 1991-04-16 1992-10-29 Rhone-Poulenc Rorer International (Holdings), Inc. Styryl-substituted heteroaryl compounds which inhibit egf receptor tyrosine kinase
US5656655A (en) * 1994-03-17 1997-08-12 Rhone-Poulenc Rorer Pharmaceuticals, Inc. Styryl-substituted heteroaryl compounds which inhibit EGF receptor tyrosine kinase
WO2006055565A3 (en) * 2004-11-19 2006-06-29 Schering Plough Ltd Control of parasites in animals by the use of parasiticidal 2-phenyl-3-(1h-pyrrol-2-yl) acrylonitrile derivatives
US20060128779A1 (en) * 2004-11-19 2006-06-15 Schering-Plough Animal Health Corporation Control of parasites in animals by the use of parasiticidal 2-phenyl-3-(1H-pyrrol-2-yl)acrylonitrile derivatives
WO2006055565A2 (en) * 2004-11-19 2006-05-26 Schering-Plough Ltd. Control of parasites in animals by the use of parasiticidal 2-phenyl-3-(1h-pyrrol-2-yl) acrylonitrile derivatives
US7705038B2 (en) 2004-11-19 2010-04-27 Intervet, Inc. Control of parasites in animals by the use of parasiticidal 2-phenyl-3-(1H-pyrrol-2-yl)acrylonitrile derivatives
US20100261698A1 (en) * 2008-06-27 2010-10-14 Christopher Adams Organic compounds
US20110082129A1 (en) * 2008-06-27 2011-04-07 Christopher Adams Organic compounds
US8030334B2 (en) 2008-06-27 2011-10-04 Novartis Ag Organic compounds
US8791141B2 (en) 2008-06-27 2014-07-29 Novartis Ag Organic compounds
US9242963B2 (en) 2008-06-27 2016-01-26 Novartis Ag Organic compounds
CN110386881A (en) * 2018-04-19 2019-10-29 中国科学院昆明植物研究所 Diaryl ethylene compounds and its pharmaceutical composition and its application
CN110386881B (en) * 2018-04-19 2021-03-02 中国科学院昆明植物研究所 Diarylethene compound, pharmaceutical composition and application thereof

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